New concepts of mechanisms of intestinal cholesterol absorption.

The small intestine is a unique organ providing dietary and reabsorbed biliary cholesterol to the body. However, the molecular mechanisms whereby cholesterol is absorbed have not yet been fully understood. Recent research suggests that the newly identified ATP-binding cassette (ABC) transporters ABCG5 and ABCG8 are apical cholesterol export pumps that promote partial efflux of cholesterol and nearly complete efflux of plant sterols from enterocytes into the intestinal lumen after their absorption. This provides an explanation why cholesterol absorption is a selective process in that plant sterols and other non-cholesterol sterols are absorbed poorly or not at all. Furthermore, a putative cholesterol import protein has been proposed, but remains uncharacterized. The identification of such a gene should yield new insights into the mechanisms that potentially regulate the influx of cholesterol across the apical brush border membrane of the enterocyte. Combination therapy using a novel and potent cholesterol absorption inhibitor (ezetimibe) and an HMG-CoA reductase inhibitor (statins) offers an efficacious new approach to the prevention and treatment of hypercholesterolemia.